Protein kinases play important roles in cellular signal pathways that regulate various cell functions such as differentiation, proliferation, migration and apoptosis. Deregulation of protein kinases is implicated in a number of diseases including cancer.
FMS-like tyrosine kinase 3 (“FLT3”), vascular endothelial growth factor (“VEGF”) receptor, and aurora kinase, are three common protein kinases.
FLT3 is a receptor tyrosine kinase. Mutations of FLT3 can lead to development of cancer, e.g., acute myeloid leukemia. See Pratz et al., Current Drug Targets, 2010, 11(7), 781-9.
VEGF is a signal protein produced by cells that stimulates the growth of new blood vessels. It stimulates cellular responses by binding to a tyrosine kinase receptor, i.e., VEGF receptor (“VEGFR”), on the cell surface, causing it to dimerize and become activated through transphosphorylation. VEGFR has been identified as the predominant regulator of tumor angiogenesis. See Hicklin et al., J Clin Oncol., 2005, 23, 1011-1027.
Aurora kinases are essential for cell proliferation. Defects in these kinases lead to severe mitotic abnormality, a condition which is highly associated with tumorigenesis. See Fu et al., Mol. Cancer Res., 2007, 5, 1-10.
These three protein kinases are attractive therapeutic targets in cancer treatment.